Altered Levels of Salivary 8-oxo-7-hydrodeoxyguanosine in Breast Cancer

2016 ◽  
Vol 1 (2) ◽  
pp. 171-177 ◽  
Author(s):  
M. Gornitsky ◽  
A.M. Velly ◽  
S. Mohit ◽  
M. Almajed ◽  
H. Su ◽  
...  

Oxidative stress has been implicated in the pathogenesis of breast cancer (BC). To determine whether BC is associated with altered salivary redox homeostasis, we performed a case-control study assessing the relationship between BC and 8-oxo-7-hydrodeoxyguanosine (8-oxodG), a marker for oxidative damage to DNA. Enzyme-linked immunosorbent assay for 8-oxodG was used on whole, unstimulated saliva of 134 BC patients and 226 healthy controls. Associations of the redox data were assessed by analysis of variance and logistic regression analysis. Our results revealed that there were 1) significantly lower mean levels of salivary 8-oxodG in BC patients versus controls ( P = 0.0005), 2) significantly lower levels among participants who did not receive radiotherapy and/or chemotherapy as compared with controls ( P < 0.0001), 3) significantly lower levels among BC patients who did not receive these treatments than among those who did ( P < 0.02), 4) and no significant differences in mean 8-oxodG levels among BC patients positive or negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 ( P ≥ 0.08). Our results suggest that BC is associated with decreased levels of oxidatively modified DNA in saliva. Knowledge Transfer Statement: The results of our current case-control study indicate that the molecular biomarker of oxidative stress 8-oxo-7-hydrodeoxyguanosine, measured from saliva, is associated with breast cancer. Our findings may provide the basis for future studies on molecular biomarkers of oxidative stress and breast cancer using saliva as an accessible and noninvasive tissue.

Author(s):  
Saman SARGAZI ◽  
Milad HEIDARI NIA ◽  
Shekoufeh MIRINEJAD ◽  
Mahdiyeh MOUDI ◽  
Mahdiyeh JAFARI SHAHROUDI ◽  
...  

Background: KIF26B gene is found to play essential roles in regulating different aspects of cell proliferation and development of the nervous system. We aimed to determine if rs12407427 T/C polymorphism could affect susceptibility to schizophrenia (SZN) and breast cancer (BC), the two genetically correlated diseases. Methods: The current case-control study was performed from Aug 2018 to Dec 2018. Briefly, 159 female pathologically confirmed BC cases referring to Alzahra Hospital, Isfahan, Iran, and 102 psychologically confirmed SZN patients (60 males and 42 females) admitted to Baharan Hospital, Zahedan, Iran, were enrolled. Using the salting-out method, genomic DNA was extracted, and variants were genotyped using allele-specific amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method. Results: The results revealed a significant association between the KIF26B rs12407427 codominant CT (P=0.001), CC (P=0.0001), dominant CT+CC, and recessive CC (P=0.001) genotypes with the risk of developing SZN. Significant correlations were also found regarding rs12407427 and BC susceptibility in different inheritance models, including over-dominant CT (P=0.026), dominant CT+CC (P=0.001), recessive CC (P=0.009), and codominant CT and CC (P=0.001) genotypes. The over-presence of the C allele was also correlated with an increased risk for SZN (P=0.0001) and BC (P=0.0001). Finally, computational analysis predicted that T/C variation in this polymorphism could change the binding sites in proteins involved in splicing. Conclusion: rs12407427 T/C as a de novo KIF26B variant might be a novel genetic biomarker for SZN and/or BC susceptibility in a sample of the Iranian population.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5509 ◽  
Author(s):  
Mohini A. Tupurani ◽  
Chiranjeevi Padala ◽  
Kaushik Puranam ◽  
Rajesh K. Galimudi ◽  
Keerthi Kupsal ◽  
...  

Background Oxidative stress (OS) is a key characteristic feature in cancer initiation and progression. Among multiple cancers, NADPH oxidase (NOX) dependent free radical production is implicated in oxidative stress. P22phox, a subunit of NADPH oxidase encoded by the CYBA gene has functional polymorphisms associated with various complex diseases. The present study was aimed to examine the importance and association of the functional polymorphisms of CYBA gene (-930 A/G and 242 C/T) with the oxidative stress in breast cancer (BC) development and progression. Materials and Methods We have performed a case-control study on 300 breast cancer patients and 300 healthy individuals as controls to examine the role of CYBA gene -930 A/G and 242 C/T single nucleotide polymorphisms (SNPs) using As-PCR and PCR-RFLP assays and its association with OS as measured by plasma MDA levels. Linkage disequilibrium (LD) plots were generated using Haploviewtool and Multifactor dimensionality reduction (MDR) analysis was applied to assess high-order interactions between the SNPs. The Insilco analysis has been performed to predict the effect of SNPs on the gene regulation using online tools. Results We have found that genotype frequencies of CYBA gene -930 A/G and 242C/T polymorphism were significantly different between controls and BC patients (p < 0.05). The haplotype combination -930G/242C and -930G/242T were associated with 1.44 & 1.56 folds increased risk for breast cancer respectively. Further, the MDA levels were higher in the patients carrying -930G/242C and -930G/242T haplotype (p < 0.001). Our results have been substantiated by Insilco analysis. Conclusion Results of the present study suggest that GG genotype of -930 A/G polymorphism, -930G/242C and -930G/242T haplotypes of CYBA gene polymorphisms have shown association with higher MDA levels in breast cancer patients, signify that elevated oxidative stress might aid in increased risk for breast cancer initiation and progression.


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